Erythrocyte aldehyde dehydrogenase activity in alcoholic subjects and its value as a marker for hepatic aldehyde dehydrogenase in subjects with and without liver disease

Erythrocyte aldehyde dehydrogenase activity was assayed in actively drinking alcoholics, patients with alcoholic liver disease who claimed to be abstaining, patients with non-alcoholic liver disorders and normal controls. Hepatic cytosolic aldehyde dehydrogenase was also assayed in the majority of the subjects. Actively drinking alcoholics had significantly lower erythrocyte aldehyde dehydrogenase activity than controls (P less than 0.01) but abstaining alcoholic liver disease and non-alcoholic liver disorder subjects did not. There was a significant correlation between erythrocyte and hepatic cytosolic aldehyde dehydrogenase activity in the control group (r = 0.94, P less than 0.05) but not in the other study groups.     

Effect of liver disorders on ethanol elimination and alcohol and aldehyde dehydrogenase activities in liver and erythrocytes

1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1.2.1.3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects. 2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities. 3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group. 4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group. 5. Hepatic ALDH activity, assayed at 300 mumol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Operant acquisition of alcohol by women

Alcohol acquisition and use patterns were studied in 26 women on a clinical research ward. Women could earn alcohol (beer, wine or distilled spirits) or 50 for 30 min of performance on a second-order fixed ratio 300 (fixed interval 1 sec: S) schedule of reinforcement. Points earned for money and for alcohol were not interchangeable. A 7-day drug-free base line was followed by 21 days of alcohol availability and a postalcohol drug-free period of 7 days. Heavy, moderate and occasional drinkers differed significantly in the average number of alcohol drinks purchased (P less than .001). Five heavy drinkers purchased an average of 164 (+/- 14) drinks during the study; 12 moderate drinkers purchased an average of 80 (+/- 4) drinks; 9 occasional drinkers purchased an average of 26 (+/- 4) drinks. Individual drinking patterns fluctuated markedly from day-to-day. Daily peak blood alcohol levels (milligrams per deciliter) were significantly correlated with variations in daily drinking patterns in 22 of the 26 subjects (P less than .02-.0001). Computer analysis of daily alcohol consumption patterns (alcohol peak frequency and peak amplitude) showed that moderate drinkers had significantly more peaks in alcohol consumption than occasional drinkers (P less than .05). The average number of drinks constituting each peak was significantly greater for the heavy and moderate drinkers than for the occasional drinkers (P less than .05). The interval between successive peaks in alcohol consumption averaged 4.6 (+/- 0.8) days for the occasional drinkers, 3.2 (+/- 0.2) days for the moderate drinkers and 3.6 (+/- 0.17) days for the heavy drinkers but these differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of age and sex on allyl alcohol hepatotoxicity in rats: role of liver alcohol and aldehyde dehydrogenase activities

Allyl alcohol-induced hepatotoxicity was more severe in old male rats than in young-adult male rats, as measured by release of hepatic enzymes from injured cells and loss of hepatic microsomal cytochrome P-450. The extent of toxicity in female rats was greater than in males and was unaffected by aging. The purpose of this study was to examine possible causes for these differences. The activity of alcohol dehydrogenase (ADH) with allyl alcohol as substrate was measured in liver cytosolic fractions of rats at ages representing young adulthood, middle age and old age. ADH activities were 1.7 +/- 0.1, 2.3 +/- 0.1 and 2.6 +/- 0.1 mumol/min/g of liver in male rats aged 4, 14 and 25 months, respectively. ADH activities in young-adult and old female rats were 3.8 +/- 0.1 and 3.7 +/- 0.1 mumol/min/g of liver. There was a good correlation (r = 0.99, P less than .001) between liver ADH activity and allyl alcohol-induced hepatotoxicity, measured as the release of sorbitol dehydrogenase into the bloodstream. Cytosolic free NAD+/NADH ratios in male rats were not significantly different among the three age groups; the ratios were lowest in young-adult female rats. Low Km aldehyde dehydrogenase activities in liver mitochondrial and cytosolic fractions were similar among the three age groups of male rats, and the activities in female rats were not substantially different. The results indicated that increased ADH activity is the principal cause of the age-associated enhancement of allyl alcohol hepatotoxicity in male rats.     

Acetaldehyde-modified hemoglobin as a marker of alcohol consumption: comparison of two new methods.

We examined the diagnostic value of acetaldehyde-hemoglobin adducts in the detection of heavy drinking and alcoholism. Acetaldehyde adducts from red cells were measured by new chromatographic and immunologic methods. The study population included 20 men with well-documented histories of chronic alcoholism, 18 men who were heavy drinkers, 22 male healthy control subjects, and 8 control subjects with liver disease that was not related to alcohol use. In addition, 20 healthy volunteers and 5 control subjects participated in the study to determine the effect of an acute dose of ethanol. The results that were obtained by the two new methods correlated significantly (r = 0.38, p = 0.002). With both methods, the concentrations of acetaldehyde-hemoglobin adducts were found to be significantly higher in red cells of heavy drinkers (p less than 0.001) and subjects with alcoholism (p less than 0.001) when compared with control subjects. Acetaldehyde-modified hemoglobins appear to have at least the same sensitivity (chromatographic determination = 50% and immunologic determination = 50%) to detect heavy drinking as the most widely accepted conventional biochemical markers of alcohol abuse, gamma-glutamyltransferase (39%) or mean corpuscular volume (17%). In a group of 20 healthy volunteers, acetaldehyde-hemoglobin adducts increased significantly even after a single high dose of ethanol (2 gm/kg), whereas there was no change in the conventional markers of alcohol consumption at the same time. Acetaldehyde-hemoglobin adducts assays should be useful for the detection of heavy drinking in clinical settings.     

Hepatic vein oxygenation, liver blood flow, and the rate of ethanol metabolism in recently abstinent alcoholic patients

Abstract. To determine whether hepatic hypoxia is associated with hepatocellular necrosis in alcoholics, oxygen tension in the hepatic vein and hepatic blood flow were determined in thirteen patients without overt clinical liver disease. Ethanol metabolic rate was also assayed as an index of liver metabolism. Hepatic blood flow and ethanol metabolic rate were also determined in six normal volunteers. According to liver histology patients were separated into two groups, with and without hepatocellular necrosis. Alcoholics with necrosis showed a higher ( P < 0–002) ethanol metabolic rate (405±0–23 mmol/kg/h) than those without necrosis (2–46±0–34). Hepatic blood flow in the total group of alcoholics was not significantly different from controls; in the group with necrosis it was lower (651-7±44-6 ml/min/m²) than in the group without necrosis (878-3±81-6; P < 0025). Hepatic vein pO₂ was lower ( P < 001) in patients with hepatocellular necrosis (31-7±0–68 mmHg) than in patients without necrosis (35-7±0–99). In the whole group, a significant negative correlation ( r = -0 76, P < 0–003) was observed between hepatic vein pO₂ and ethanol metabolic rate. Acute administration of ethanol (21-7 mmol/kg) did not alter hepatic blood flow in six normal individuals nor in five alcoholic patients, although an increase in hepatic vein pO₂ was observed in the latter. The changes observed in hepatic vein pO₂, functional hepatic blood flow, and ethanol metabolic rate which correlate with hepatocellular necrosis, may be of pathogenic importance in alcoholic liver disease.     

Changes in serum enzymes in moderate drinkers after an alcohol challenge

When 14 "moderate" drinkers abstained from alcohol for four weeks, the activity of gamma-glutamyltransferase (GGT; EC 2.3.2.2) in their serum showed a large decrease. Immediately after the period of abstention, an orally given ethanol challenge of 1 g/kg produced a marked increase in serum GGT at 24 h, followed by a slow decline thereafter. Aspartate amino-transferase activity in serum was significantly increased at 24 h; however, alkaline phosphate, alanine aminotransferase, and lactate dehydrogenase showed much smaller or no changes. An abnormal increase in lactate dehydrogenase isoenzyme 5 was observed in seven subjects. In some of the moderate drinkers, liver biopsies showed mild chronic hepatitis or nonspecific changes. Eight nondrinking controls showed only slight increases in serum GGT following the same alcohol challenge; results for the other enzyme tests were unchanged. We consider it probable that pre-existing liver disease affects the response to ethanol, so that greater amounts of GGT are released from hepatic tissue; alternatively, drinkers may have a higher GGT activity in this tissue as a result of enzyme induction by ethanol. The alcohol challenge test was an effective discriminator between moderate drinkers and abstainers.     

1-14C]Ethanol breath test in alcoholic liver disease

The activity of ethanol metabolising enzymes was assessed in 51 patients with alcoholic and non-alcoholic liver disease using tracer doses of [1-14C]ethanol and measuring 14CO2 excretion in the breath. Alcoholic patients with only fatty infiltration of the liver showed significantly increased activity compared with controls. Comparing alcoholic patients with cirrhosis and a serum albumin greater than 28 g/l, activity in those with a recent history of continued heavy drinking was significantly greater than in patients who had abstained from alcohol. In addition, both groups of alcoholic cirrhosis showed significantly more activity than patients with non-alcoholic cirrhosis. The activities of patients with acute alcoholic or viral hepatitis were normal when their prothrombin times were less than 7 sec prolonged, but were reduced when prolongation exceeded 7 sec. These results demonstrate that in chronic alcoholic liver disease, even with cirrhosis, alcohol can still increase the activity of ethanol oxidising enzymes provided hepatic function remains adequate. However, this response is lost in acute liver damage and in chronic alcoholic disease with severe hepatic dysfunction.     

Hepatic vein oxygenation, liver blood flow, and the rate of ethanol metabolism in recently abstinent alcoholic patients

Abstract To determine whether hepatic hypoxia is associated with hepatocellular necrosis in alcoholics, oxygen tension in the hepatic vein and hepatic blood flow were determined in thirteen patients without overt clinical liver disease. Ethanol metabolic rate was also assayed as an index of liver metabolism. Hepatic blood flow and ethanol metabolic rate were also determined in six normal volunteers. According to liver histology patients were separated into two groups, with and without hepatocellular necrosis. Alcoholics with necrosis showed a higher ( P < 0–002) ethanol metabolic rate (405 ± 0–23 mmol/kg/h) than those without necrosis (2–46 ± 0–34). Hepatic blood flow in the total group of alcoholics was not significantly different from controls; in the group with necrosis it was lower (651–7 ± 44–6 ml/min/m²) than in the group without necrosis (878–3 ± 81–6; P < 0025). Hepatic vein pO₂ was lower ( P < 001) in patients with hepatocellular necrosis (31–7 ± 0–68 mmHg) than in patients without necrosis (35–7 ± 0–99). In the whole group, a significant negative correlation ( r = -0 76, P < 0–003) was observed between hepatic vein pO₂ and ethanol metabolic rate. Acute administration of ethanol (21–7 mmol/kg) did not alter hepatic blood flow in six normal individuals nor in five alcoholic patients, although an increase in hepatic vein pO₂ was observed in the latter. The changes observed in hepatic vein pO₂, functional hepatic blood flow, and ethanol metabolic rate which correlate with hepatocellular necrosis, may be of pathogenic importance in alcoholic liver disease.     

Role of the liver in alcohol-induced alteration of high-density lipoprotein metabolism

The effect of alcohol intake on the serum levels of high-density lipoprotein cholesterol (HDL-ch), apoprotein A-I (apo A-I), and apoprotein A-II (apo A-II) was investigated in 15 habitual alcohol drinkers without liver injury (group A), 17 with mild hepatic damage (group B), and five with advanced liver disease (group C). The serum level of HDL-ch was higher in group A than in 10 nondrinkers (P less than 0.01) but lower in group B (P less than 0.05) and markedly lower in group C (P less than 0.01). The level of apo A-I was also higher in group A (P less than 0.05), although the level of apo A-II was not. To elucidate the effect of alcohol on apo A-I production by hepatocytes, the synthesis of apo A-I and albumin by cultured rat liver cells in the presence of ethanol was also investigated. Ethanol enhanced the production of apo A-I but not that of albumin. The results suggest that serum HDL is elevated in habitual alcohol drinkers without liver injury and that the elevation of HDL in blood is mainly dependent on the increase of apo A-I synthesis in the liver.     

Circulating endogenous vasoactive intestinal polypeptide (VIP) in patients with uraemia and liver cirrhosis

The concentration of vasoactive intestinal polypeptide (VIP) in peripheral venous plasma was median 6.0 pmol l-1 (range 0-20) in 112 normal subjects. In fifty-three patients with decreased kidney function plasma VIP was significantly increased (median 15.0 pmol l-1, range 0.5-70, P less than 0.0001) and positively correlated to serum creatinine concentration (r = 0.51, P less than 0.001). In 133 patients with liver cirrhosis peripheral venous VIP was slightly elevated (median 7.0 pmol l-1 range 0-86, P less than 0.01). Samples obtained during a central venous catheterization showed significant renal extraction of circulating VIP in control subjects (median extraction fraction 23%, P less than 0.05, n = 6) and in patients with cirrhosis (median 60%, P less than 0.02, n = 8), but not in uraemic patients (median 0%, NS n = 5). In control subjects and patients with cirrhosis the concentration of VIP in the hepatic vein was significantly below that of systemic plasma (-42%, P less than 0.05, n = 6 and -45%, P less than 0.01, n = 10, respectively). On the contrary, in uraemic patients hepatic venous VIP was almost similar to systemic VIP (-4%, NS, n = 7). The results indicate that in normal subjects and patients with cirrhosis both the liver and kidneys are involved in the biodegradation of VIP. The elevated level of circulating VIP in uraemic patients may in part be due to decreased renal and hepatic biodegradation but increased neuronal release of VIP, especially in the splanchnic system, may also contribute to the increased plasma VIP in this condition.     

Hyperlipidaemia in gout.

Significant elevations of plasma triglyceride and free fatty acids levels were shown in 107 gouty patients, but no significant difference was found in plasma cholesterol and phospholipid levels as compared with control subjects. A positive correlation was found between plasma triglyceride and free fatty acids levels (r = 0.249, P less than 0.05) in gouty patients. The heavy drinkers with gout (15.9% of the patients) had significantly higher plasma triglyceride, free fatty acids and gamma-glutamyltranspeptidase levels than the moderate or non-drinking gouty subjects. These results suggested that excessive intake of alcohol may play an important role in inducing hyperlipidaemia in gout.     

Total fasting serum bile acids and beta-hexosaminidase in alcoholic liver disease

Total serum bile acid levels and beta-hexosaminidase activity were studied in 22 normal subjects, 35 non-cirrhotic patients with acute alcohol intoxication, 45 patients with alcoholic liver cirrhosis and 11 patients with alcoholic liver cirrhosis and surgical portal-systemic shunts. Comparison was made with traditional liver function tests. beta-Hexosaminidase was most frequently elevated in acute alcohol intoxication (94%) while total serum bile acids were elevated in all patients with alcoholic liver cirrhosis. Total serum bile acid levels were found to discriminate most efficiently between acute alcohol intoxication and liver cirrhosis. The combined determination of serum beta-hexosaminidase and total serum bile acids is proposed for evaluating alcoholic liver disease.     

Serum low density lipoprotein of alcoholic patients is chemically modified in vivo and induces apolipoprotein E synthesis by macrophages.

This work was carried out to investigate the effect of alcohol drinking on serum LDL. Agarose gel electrophoresis showed that LDL samples from alcoholic patients without serious liver disease were more negatively charged and moved faster toward the cathode than LDL from nondrinking control subjects. Rabbit antibodies raised by using keyhole limpet hemocyanin modified in vitro by 4-hydroxynonenal or by acetaldehyde as immunogens reacted more strongly with patients' LDL than with control LDL, indicating the presence of oxidatively modified epitopes and acetaldehyde adducts in alcoholic patients' LDL. LDL of alcoholic patients has decreased vitamin E contents. The electromobility of LDL decreased after abstinence from alcohol and returned to normal in 2 wk, but this was not accompanied by a significant increase in its vitamin E contents. When incubated with mouse peritoneal macrophages, patients' LDL induced apolipoprotein E secretion by threefold over control LDL with a concomitant increase in cellular cholesterol. Our results thus demonstrate that LDL of alcoholic patients has lower vitamin E content, is chemically modified in vivo, and exhibits altered biological function. These changes in heavy alcoholic drinkers may render LDL more atherogenic and thereby may counter the antiatherosclerosis effects of moderate alcohol consumption.     

Fasting plasma somatostatin in alcoholic liver disease

Fasting level of somatostatin-like immunoreactivity (SLI) in plasma was measured by a highly sensitive radioimmunoassay in 36 patients with alcoholic liver disease verified by histopathology (10 patients with steatosis and 26 with cirrhosis of the liver). The median value of SLI was markedly elevated in patients with steatosis of the liver as compared to normal subjects, P less than 0.01, while the median value of SLI in the cirrhotic group was even higher, P less than 0.05, as compared to the steatotic group. Correlations of SLI to se-bilirubin and p-coagulation factors 2, 7 and 10 were significant, P less than 0.001 and P less than 0.01, respectively, whereas no correlation to plasma insulin could be elicited. These results suggest that in alcoholic liver disease fasting plasma somatostatin is correlated to the degree of hepatic failure and indicate that the liver is an important site for clearance of portal vein somatostatin.     

Influence of alcohol use, ethnicity, age, gender, BMI and smoking on the serum transferrin glycoform pattern: implications for use of carbohydrate-deficient transferrin (CDT) as alcohol biomarker

BACKGROUND: An alcohol-induced change in the serum transferrin glycoform pattern, carbohydrate-deficient transferrin (CDT), is used as a biomarker for detection and follow-up of heavy alcohol consumption. Besides studying the effects of drinking, this study evaluated any baseline differences in the transferrin pattern in relation to ethnicity, age, gender, body mass index (BMI) and smoking, as these could be confounders causing bias in CDT testing. METHODS: The transferrin glycoform pattern was determined in 1387 sera (68% men, 32% women) collected in Australia, Brazil, Canada, Finland and Japan from subjects classified as non-drinkers, light/moderate drinkers, or heavy drinkers by use of the WHO/ISBRA Interview Schedule. The iron-saturated glycoforms were separated by an HPLC candidate reference method, and the relative amounts of individual glycoforms to total transferrin were determined. RESULTS: In non-drinkers, the differences in the serum transferrin glycoform pattern in relation to ethnicity, age, gender and BMI were small and mostly not statistically significant. A higher disialotransferrin level in smokers compared with non-smokers could largely be explained by a higher alcohol intake in smokers. In the drinking subgroups, the main CDT glycoform disialotransferrin showed a positive correlation (r=0.80) with asialotransferrin, and disialo- and asialotransferrin a negative correlation with tetrasialotransferrin, that was dependent on the alcohol consumption level. CONCLUSIONS: With respect to CDT testing, the results indicated that adjustment of reference intervals for disialotransferrin and CDT in relation to ethnicity, age, gender, BMI and smoking is not required.     

Relationships among alcohol drinking, blood pressure and serum cholesterol in healthy young women

BACKGROUND: Habitual alcohol drinking affects both blood pressure and serum lipids. I investigated the relationships among alcohol drinking, blood pressure and atherogenic index defined by serum total and HDL cholesterol levels in young women. METHODS: The subjects were young (20-39 y) healthy female workers (n=7887) receiving annual health checkups. Blood pressure was compared in subjects divided into groups according to average daily alcohol consumption (non-drinkers; light drinkers, <15 g/day ethanol; moderate-to-heavy drinkers, > or =15 g/day ethanol) and in subjects divided into tertile groups of atherogenic index calculated as (total cholesterol-HDL cholesterol)/HDL cholesterol. RESULTS: When overall subjects were analyzed, systolic and diastolic blood pressure in light and moderate-to-heavy drinkers was not significantly different from that in non-drinkers. Total cholesterol levels and atherogenic index were significantly lower and HDL cholesterol was significantly higher in the light and moderate-to-heavy drinker groups than in the non-drinker group. Atherogenic index and HDL cholesterol were also significantly lower and higher, respectively, in the moderate-to-heavy drinker group than in the light drinker group. In the lowest tertile group of atherogenic index, systolic and diastolic blood pressure after adjustment for age, body mass index, smoking history and atherogenic index was significantly higher in the moderate-to-heavy drinker groups than in the non-drinker group, while systolic and diastolic blood pressure was not different among the 3 alcohol consumption groups in the highest tertile group of atherogenic index. In non-, light and moderate-to-heavy drinker groups, systolic and diastolic blood pressure was significantly higher in the highest tertile group of atherogenic index than in the lowest and middle tertile groups. CONCLUSION: Habitual alcohol drinking is related to blood pressure in young women with low atherogenic index but not in those with high atherogenic index, while blood pressure is associated with atherogenic index independently of alcohol drinking.     

Relation of drinking alcohol to atherosclerotic risk in type 2 diabetes

OBJECTIVE: The effects of drinking alcohol on atherosclerotic risks were investigated in 194 type 2 diabetic patients to determine whether drinking alcohol influences risk of atherosclerosis in diabetic subjects. RESEARCH DESIGN AND METHODS: The subjects were divided by the degree of their average weekly alcohol consumption into three groups: nondrinkers, light drinkers (ethanol consumption <210 g/week), and heavy drinkers (ethanol consumption > or = 210 g/week). The degree of atherosclerotic progression was evaluated using aortic pulse wave velocity (a-PWV), and possible atherosclerotic risks were evaluated using known atherosclerotic risk factors. RESULTS: a-PWV was significantly lower in light drinkers than in nondrinkers and heavy drinkers, but there was no significant difference in a-PWV between nondrinkers and heavy drinkers. Systolic blood pressure, HDL cholesterol, and triglyceride levels were significantly higher in heavy drinkers than in nondrinkers and light drinkers, whereas there was no significant difference in these levels between nondrinkers and light drinkers. The mean levels of BMI and blood HbA(1c), uric acid, and fibrinogen were not different between the three groups. There were significant positive correlations of a-PWV with age and systolic blood pressure and weak but significant negative correlations of a-PWV with alcohol consumption and HDL cholesterol level. CONCLUSIONS: Light drinking, but not heavy drinking, has preventive effects on atherosclerosis in type 2 diabetic subjects. The known beneficial effects of drinking alcohol on blood lipids and fibrinogen may not be involved in the preventive effect of light drinking on atherosclerosis in diabetic subjects.     

gamma-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity

gamma-Glutamyl transpeptidase activity was measured in liver and serum from 110 patients undergoing diagnostic liver biopsy, including patients with alcoholic liver disease, fatty liver not due to alcohol, primary biliary cirrhosis, persistent hepatic disease, chronic active hepatitis and normal livers. Serum gamma-glutamyl transpeptidase was markedly elevated in patients with alcoholic liver disease and primary biliary cirrhosis while mean hepatic gamma-glutamyl transpeptidase activity was significantly increased only in the alcoholic liver disease group. There was considerable overlap of individual enzyme values among the different disease groups. There was no inhibitors or activators of liver gamma-glutamyl transpeptidase in any of these disorders. The increased liver activity was not related to the degree of hepatic fibrosis or cirrhosis. There was no correlation between hepatic and serum gamma-glutamyl transpeptidase activity. Hepatic and serum gamma activities were equally increased in individuals with alcoholic liver disease whether or not they were drinking at the time of the study. The data suggest that increased hepatic gamma-glutamyl transpeptidase activity is neither specific for alcoholic liver disease nor essential for serum GGTP to be elevated.